We performed mutational analysis and transcriptome analysis of coincident ductat and acinar adenocarcinoma, along with immunohistochemical analysis of protein expression. We found shared mutations in the different histologies, suggesting ductal and acinar histologies arise from the same cell of origin. Protein and RNA expression indicate there is similar expression of the Androgen Receptor (AR) and AR-activation pathways. Ductal histology, however, was enriched for alterations in the tumor suppressor gene PTEN, as well as WNT-pathway alterations, and alterations in these major cancer-associated pathways were mutually exclusive. Our results suggest that activation of either of two independent signaling pathways can promote ductal histology, and that ductal tumors may respond to inhibitors of these pathways.